The natural hormone, 1.alpha.,25-dihydroxyvitamin D.sub.3 and its analog in ergosterol series, i.e. 1.alpha.,25-dihydroxyvitamin D.sub.2 are known to be highly potent regulators of calcium homeostasis in animals and humans, and more recently their activity in cellular differentiation has been established, V. Ostrem et al, Proc. Natl. Acad. Sci. USA, 84, 2610 (1987). Many structural analogs of these metabolites have been prepared and tested, including 1.alpha.-hydroxyvitamin D.sub.3, 1.alpha.-hydroxyvitamin D.sub.2, various side chain homologated vitamins and fluorinated analogs. Some of these compounds exhibit an interesting separation of activities in cell differentiation and calcium regulation. This difference in activity may be useful in the treatment of a variety of diseases as renal osteodystrophy, vitamin D-resistant rickets, osteoporosis, psoriasis, and certain malignancies.
Recently, 1.alpha.,25-dihydroxyvitamin D.sub.3 analogs modified at the C-18 position has been described, i.e. 18-acetoxy derivatives Maynard et al., J. Org. Chem., 57, 3214 (1992), 18-methyl, 18-hydroxy and 13-vinyl analogs Nilsson et al., Bioorg. Med. Chem. Lett., 3, 1855 (1993). The two latter analogs are potent stimulators of cell differentiation with rather low in vitro calciotropic activity.
In a continuing effort to explore new classes of pharmacologically important vitamin D compounds, analogs lacking the C-18 angular methyl group, i.e. 18-nor-vitamin D compounds have now been synthesized and tested.